Abstract: There exists a vast amount of literature spanning both pre-clinical and clinical studies indicating that changes in both hypoxia and angiogenesis impact the efficacy of conventional and targeted tumor treatments. Since current non-invasive methods to detect these physiological endpoints are either very expensive for routine use or cannot be used repeatedly since they require administration of exogenous contrast agents, there is a strong rationale to develop non-invasive methods that can inexpensively and repeatedly be used to measure these endpoints in solid tumors undergoing treatments. The main goal of this application is to detect longitudinal changes in biomarkers obtained using diffuse optical spectroscopy and to determine if these markers can act as early predictors of treatment response in solid head and neck tumors that are undergoing chemo- and/or radiotherapy. The specific aims are to: (1) evaluate the ability of optical biomarkers to indicate early response in murine tumor models of head and neck cancers when treated with single or fractionated curative doses, (2) improve the existing optical instrumentation to provide increased depth sensitivity and high portability for clinical use, (3) detect physiological endpoints of tumor hypoxia, angiogenesis and necrosis in human head and neck tumors via comparison to the gold standard of pathology, and (4) explore the ability of serial optical measurements to forecast complete radiological response vs. residual disease in human patients undergoing treatments for head and neck cancer. These studies will establish the utility of optical spectroscopy as a practical clinical tool to assess early responses in head and neck tumors to conventional treatments. The candidate will be mentored by Drs. Mark Dewhirst and Nimmi Ramanujam, and co-mentored by Drs. James Oleson and Walter Lee who are experts in the fields of cancer biology and biomedical optics, radiation oncology and head and neck surgery, respectively. This multi-disciplinary environment will provide excellent opportunities for professional growth and scientific advancement.